The I/O characterization of the Drosophila antennal lobe described in this proposal is made possible by 2 key enabling tools (i) the genetic identification of the projection neurons and the glomeruli they innervate and, (ii) multi-input/multi-output (MIMO) modeling of odor signal processing in the antennal lobe. Both tools have recently been advanced by the authors. The antennal lobe and its function are described in the MIMO model by a transfer function matrix. Our goal is to identify the transfer matrix and construct in silico a circuit diagram with the same matrix that is capable of predicting the spatio-temporal I/O dynamics of the antennal lobe. The MIMO model serves as a common language between theorists and experimentalists, and provides a framework within which to devise relevant questions and design experiments to answer those questions. For example, are there equivalent I/O characterizations of the antennal lobe that exhibit a lower complexity? We shall investigate such characterizations by (i) analyzing the representation of odor information by an arbitrary subset of olfactory sensory neurons expressing the same receptor, and (ii) studying spatial filtering methods among these neurons as a model of odor signal processing. Through genetic manipulation of the fly olfactory system, odor receptors will be expressed in olfactory sensory neurons connected to designated glomeruli. By silencing most of the remaining OSNs, these glomeruli will be effectively isolated from the rest of the antennal lobe. This will provide us with an 'in-vivo experimental platform'for investigating the I/O characteristics of the fly antennal lobe. The platform will enable us for the first time to functionally characterize all individual projection neurons innervating the same glomerulus. We shall investigate whether they are biophysically equivalent and whether they carry equivalent odor information. We will also characterize their image as a function of the number of active OSNs. We will extract the transfer matrix of a single glomerulus and of a network of 2 glomeruli isolated from the rest of the antennal lobe. We plan to quantitatively characterize the inhibition and feedback induced by the local/projection neurons on the transfer function within the same glomerulus. We also plan to measure what effect inhibition and feedback have on other glomeruli. Elucidation of odor signal processing in the antennal lobe could reveal methods of treatment of olfactory deficits. It could also reveal fundamental mechanisms of neural coding in other sensory systems.